Kidney disease is a general term, which describes a class of conditions in which the kidneys fail to filter and remove waste products from the blood. There are two forms of kidney disease; acute kidney injury (AKI) and chronic kidney disease (CKD). CKD is usually asymptomatic, except in its most advanced state. Consequently, blood and/or urine tests generally are required to make a diagnosis.
The definition of CKD developed by the Kidney Disease Outcomes Quality Initiative (KDOQI) was:                1. Kidney damage present for at least 3 months, as defined by structural or functional abnormalities (most often based on increased albuminuria e.g. urinary albumin/creatinine ratio [UACR]≥30 mg/g) and/or        2. Glomerular filtration rate (GFR)<60 mL/min/1.73 m2 present for at least 3 months.        
Within this framework, KDOQI then classified CKD into five stages, as follows:                Stage 1: Kidney damage with GFR≥90 mL/min/1.73 m2.        Stage 2: Kidney damage with GFR 60-89 mL/min/1.73 m2.        Stage 3: GFR 30-59 mL/min/1.73 m2.        Stage 4: GFR 15-29 mL/min/1.73 m2.        Stage 5: GFR<15 mL/min/1.73 m2 or kidney failure treated by dialysis or transplantation.        
In the United States, based on data from the 1999-2006 National Health and Nutrition Examination Survey (NHANES) study, an estimated 11.1 percent (22.4 million) of adults aged 20 or older have CKD stages 1-3. An additional 0.8 million U.S. adults aged 20 or older have CKD stage 4, and more than 0.3 million have stage 5 CKD and receive hemodialysis.
Analyses of NHANES data between 1988-1994 and 1999-2004 suggest that the prevalence of CKD is rising for every CKD stage, but with a particular increase in the prevalence of individuals classified with CKD stage 3. The number of patients with stage 5 CKD requiring dialysis also has increased. It has been estimated that more than 700,000 individuals will have End Stage Renal Disease (ESRD) by 2015.
Although CKD can be caused by primary kidney disease (e.g. glomerular diseases, tubulointerstitial diseases, obstruction, and polycystic kidney disease), in the vast majority of patients with CKD, the kidney damage is associated with other medical conditions such as diabetes and hypertension. In 2008, excluding those with ESRD, 48 percent of Medicare patients with CKD had diabetes, 91 percent had hypertension, and 46 percent had atherosclerotic heart disease. Other risk factors for CKD include age, obesity, family history, and ethnicity.
CKD has been associated with numerous adverse health outcomes. Many studies have reported that a GFR of 30-59 mL/min/1.73 m2 is associated with an increased risk of mortality, cardiovascular disease, fractures, bone loss, infections, cognitive impairment, and frailty. Similarly, there appears to be a graded relationship between the severity of proteinuria or albuminuria and adverse health outcomes, including mortality, ESRD, and cardiovascular disease. Further, the risk for adverse outcomes conferred by reduced GFR and increased albuminuria (or proteinuria) appears to be independent and multiplicative.
The rationale for considering screening for early-stage CKD includes the high and rising prevalence of CKD, its known risk factors, its numerous adverse health consequences, its long asymptomatic phase, the availability of potential screening tests for CKD, and the availability of treatments that may alter the course of early-stage CKD and reduce complications of early-stage CKD or its associated health conditions.
Some organizations already recommend CKD screening in selected populations. Kidney Disease: Improving Global Outcomes (KDIGO) recommends screening of all patients with hypertension, diabetes, or cardiovascular disease. The American Diabetes Association recommends annual screening of all adults with diabetes, based on “expert consensus or clinical experience.” The Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC7) recommends annual screening of all patients with combined hypertension and diabetes. Also advocating selected screening, the National Kidney Foundation sponsors free CKD screening for all adults with hypertension, diabetes, or a primary relative with a history of kidney disease, hypertension, or diabetes.
In most patients with CKD stages 1 to 3 GFR declines slowly. However, the rate of decline varies among individuals, and many factors appear to impact progression. Because CKD stages 1 and 2 usually progress asymptomatically, detection of early-stage CKD requires laboratory testing.
Some organizations recommend monitoring for changes in kidney function or damage in patients with CKD. For example, the Kidney Disease Outcomes Quality Initiative (KDOQI) recommends at least annual estimated GFR measurement in adults with CKD in order to predict onset of ESRD and evaluate the effect of CKD treatments. JNC7 recommends annual quantitative measurement of albuminuria in all patients with “kidney disease.” KDOQI also recommends more frequent monitoring of CKD patients with worsening kidney function.
Despite the importance of measuring clinical parameters for CKD in serum or urine, there are few diagnostic tests to detect early stage CKD and monitor the progression of this disease. Measurement of GFR is not sufficiently sensitive for early detection of kidney disease, while the measurement of urinary protein is not specific for kidney disease, nor is it suitable for monitoring the progression of the disease. Therefore, there is a requirement for a specific and sensitive clinical marker or combination of markers for the diagnosis of early CKD and staging of kidney disease.